Pharmaceutical agents can be encapsulated in either a hard or soft gelatin shell. Hard gelatin capsules are filled with dry materials such as powders or time-release beadlets by introducing the material into one section of the capsule and capping it with a second section. The shell of a hard gelatin capsule is not plasticized, unlike that of a soft gelatin capsule, which is plasticized by the addition of glycerin, sorbitol, or a similar polyol. Instead of dry materials, soft gelatin capsules generally enclose a fluid or semi-fluid fill material or "vehicle" in which the active ingredient is dispersed or dissolved.
Soft gelatin encapsulation of a solution or dispersion of a pharmaceutical agent in a liquid vehicle or carrier offers many advantages over other dosage forms such as compressed, coated or uncoated solid tablets or bulk liquid preparations. Gelatin encapsulation of a solution or dispersion permits accurate delivery of a unit dose, an advantage which becomes especially important when relatively small amounts of the active ingredient must be delivered, as in the case of certain hormones. Such uniformity is more difficult to achieve via a tabletting process wherein solids must be uniformly mixed and compressed, or via incorporation of the total dose of active ingredient into a bulk liquid carrier which must be measured out prior to each oral administration. Soft gelatin capsules are also more easily transported by patients than bulk liquids, since only the required number of doses need be removed from the package.
Soft gelatin encapsulation further provides the potential to improve the bioavailability of pharmaceutical agents. Relatively insoluble active ingredients can be dispersed in a liquid or gelled carrier to provide faster absorption upon rupture of the capsule. For example, Miskel et al. (U.S. Pat. No. 3,851,051) disclose soft gelatin capsules which contain aqueous solutions or suspensions of active ingredients in a water-soluble gel lattice matrix which is formulated to rapidly disperse upon rupture of the capsule shell.
A well-recognized difficulty in the art of soft gelatin encapsulation is that the gelatin capsule shell can be deleteriously effected by water or other aqueous solvents present in the capsule fill material. One way in which previous investigators have addressed the problem of the delivery of an aqueous fill material in a water soluble capsule shell has been by modifying the composition of the shell. For example, the shells of soft gelatin capsules have been modified in order to produce an increased stability of the shell to withstand dissociation by an aqueous capsule fill material. Szymanski et al. (U.S. Pat. No. 3,865,603) disclose gelatin compositions which are "extended" by adding to the gelatin of the shell fluidity starches and thermally modified starches, both of which are chemically modified by the addition of monoreactive moieties.
Kreuger (U.S. Pat. No. 2,580,683) discloses the addition of non-hygroscopic water soluble substances (i.e., substances whose physical characteristics will not be appreciably altered by the effects of water vapor) to the shell of gelatin capsules which have been filled with aqueous solutions of an ingredient compounded with a hygroscopic substance. Sugars are disclosed as the preferred non-hygroscopic constituent of the capsule wall. Raising the sugar content of the capsule wall is disclosed as a means of reducing the required content of dry material in the fill.
Morishita (Japanese Application No. 56-89833) discloses a shell material formed from gelatin, tannic acid, water, and "sugar-type ethyl alcohol, grape sugar, or a similar sugar." Morishita further discloses that this acidic shell encloses a non-acidic filler.
Kobayashi (U.S. Pat. No. 730,926) discloses a soluble, filmy substance used as a wrapper for medicines, either powders or pills, which comprises isinglass or gelatin, starch, and water. A film of "substantially equal parts" of starch and gelatin is disclosed which is made of edible ingredients, and which is soluble in saliva or gastric juice. The film disclosed by Kobayashi is used by wrapping it around medicines, and then putting the wrapped medicine in water, so that the film swells and softens.
The soft gelatin-based compositions commonly employed to form the shells of soft gelatin capsules are not palatable or edible as those terms are understood in the art. Although they are not toxic, most shells yield a gummy, unpleasant tasting, intractable mass in the mouth if they are chewed. However, a gelatin shell which is chewable and edible in the sense that it is pleasant tasting and can be readily fragmented, dissolved, and swallowed would be advantageous for a number of reasons.
For example, in instances where a user is in medical distress from the sudden attack of a condition such as angina pectoris, rapid release of the active ingredient in the fill material of a capsule into the mouth is essential. The shell of a capsule must dissolve rapidly, without leaving any intractable, insoluble residue in the mouth upon which the distressed user might choke. Additionally, when the active ingredients are palatable and thus need not be swallowed whole, soft gelatin capsules provide a convenient delivery vehicle for a unit dosage of the active ingredient. Children and elderly users may not be able to swallow entire capsules, tablets, or pills. Soft gelatin capsules allow these users to easily chew and ingest the active ingredients within the capsules in a palatable form.
Therefore, a need exists for a soft gelatin capsule comprising a shell which is readily chewable and edible.